Functional polymorphisms in ACE and CYP11B2 genes and atrial fibrillation in patients with hypertensive heart disease

Huang, Mingfang; Gai, Xiaowu; Yang, Xiangyue; Hou, Jianping; Lan, Xiaopeng; Zheng, Weixing; Chen, Fengping; He, Jiake

doi:10.1515/cclm.2009.023

Cited by 18 publications

(20 citation statements)

References 37 publications

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“…Although the sample size of our study was larger than the studies in Chinese Taiwan and Turkish population, we still need to verify the result in a more large-scale population. Other studies revealed that-344C/T (rs1799998) of CYP11B2 was associated with AF risk [12, 13, 14]. In our study, the single “A” mutation of CYP11B2 rs3802230 in the diplotype analysis, which was no genetic linkage with reported polymorphisms, showed reduced risk of AF.…”

Section: Discussionsupporting

confidence: 45%

Polymorphisms of Renin-Angiotensin-Aldosterone System Gene in Chinese Han Patients with Nonfamilial Atrial Fibrillation

et al. 2015

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BackgroundAtrial fibrillation(AF) is the most common arrhythmia in the adult population. The activated renin-angiotensin-aldosterone system (RAS) has been reported to play an important role in the pathogenesis of atrial fibrillation. The aim of this study was to investigate the association between nonfamilial AF and polymorphisms in RAS gene.MethodsA total of 931 patients with nonfamilial AF, 663 non-AF heart disease patients and 727 healthy subjects were selected. 10 tagSNPs (tSNPs) (ACE gene rs8066114, AGT gene rs7539020, rs3789678, rs2478544, rs11568023, rs2478523, rs4762, rs699 and CYP11B2 rs3802230, rs3097) were chosen and genotyped in our study. Single-locus analysis and haplotype analysis were used in this study.ResultsIn single-locus analysis, we found rs11568023 and rs3789678 in AGT gene were associated with nonfamilial AF in Chinese Han population. AF risk was associated with rs3789678 between the AF group and control groups. Under dominant model, the significant AF risk was observed in rs3789678 between the AF group and non AF heart control group; And the protective effect was found in rs11568023, compared with the non-AF heart disease control group. In multilocus haplotype analysis, the association between frequencies of the haplotypes and AF risk was showed in AGT gene (rs7539020-rs3789678), compared ‘TT’ haplotype with the common ‘TC’ haplotype, adjusted for age, gender, LVEF, LVEDD, LAD and frequency of hypertension and diabetes. The diplotype with ‘TC’, carrying rs3789678-C-allele, was associated with reduced risk of AF between the AF group and the healthy control group. The diplotype with ‘TT’ haplotype in the same block, carrying rs3789678-T-allele, was associated with increased risk of AF.ConclusionsVia a large-scale case-control study, we found that rs3789678 site was potential susceptible locus of AF whereas rs11568023 was protective factor.

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Section: Discussionsupporting

confidence: 45%

Polymorphisms of Renin-Angiotensin-Aldosterone System Gene in Chinese Han Patients with Nonfamilial Atrial Fibrillation

et al. 2015

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“…Most of the examined genes are associated with the renin-angiotensin system and results have been conflicting. The LA size was larger in individuals who were homozygous for the insertion polymorphism of the angiotensin converting enzyme in Turkish hypertensive patients 15 but not in Chinese patients14. No association was found between LA size and the −344T/C polymorphism in the aldosterone synthase (CYP11B2) gene in patients with heart failure 17.…”

Section: Discussionmentioning

confidence: 95%

A Comprehensive Genetic Study on Left Atrium Size in Caribbean Hispanics Identifies Potential Candidate Genes in 17p10

Wang

Tullio

Beecham

et al. 2010

Circ Cardiovasc Genet

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Background-Left atrial (LA) enlargement is associated with cardiovascular disease and stroke. Genetic factors contributing to the LA dimension are poorly understood. We sought to map susceptibility genes for LA size in a large Dominican family data set and an independent population-based sample from the Northern Manhattan Study. Methods and Results-One hundred Dominican families comprising 1350 individuals were studied to estimate heritability and map quantitative trait loci for LA size using variance components analysis. LA dimension was measured by transthoracic echocardiography. A polygenic covariate screening was used to identify significant covariates. LA size had a moderate estimate of heritability (h 2 ϭ0.42) after adjusting for significant covariates. Linkage analysis revealed suggestive evidence on chromosome 10p19 (D10S1423, MLODϭ2.00) and 17p10 (D17S974, MLODϭ2.05). Ordered subset analysis found significantly enhanced (PϽ0.05 for increase of LOD score) evidence for linkage at 17p10 (MLODϭ2.9) in families with lower LDL level. Single nucleotide polymophisms (nϭ2233)were used to perform a peak-wide association mapping across 17p10 in 825 NOMAS individuals. Evidence for association were found in NTN1, MYH10, COX10, and MYOCD genes (Pϭ0.00005 to 0.005). Conclusions-Using nonbiased genome-wide linkage followed by peak-wide association analysis, we identified several possible susceptibility genes affecting LA size. Among them, MYOCD has been shown to serve as a key transducer of hypertrophic signals in cardiomyocytes. Our data support that polymorphisms in MYOCD modify LA size. (Circ Cardiovasc Genet. 2010;3:386-392.)Key Words: left atrium Ⅲ genetics Ⅲ myocardin Ⅲ MYH10 Ⅲ COX10 L eft atrial (LA) enlargement has been associated with increased mortality in high-risk patients with left ventricular dysfunction 1 or atrial arrhythmias 2 but also in the general population. 3,4 An enlarged LA is also associated with the development of atrial fibrillation, 5,6 a strong determinant of ischemic stroke and death. 3,4,7 Even among subjects without atrial fibrillation, LA enlargement has been associated with an increased risk of ischemic stroke. 8 -10 We have previously shown an increased stroke risk in subjects with increased LA size, whether measured directly by echocardiography 10 or inferred by electric abnormalities detected on ECG. 11 Clinical Perspective on p 392Multiple conditions have been associated with LA enlargement, 12 including mitral valve disease, arterial hypertension, and any condition that increases the left ventricular filling pressures. 12 Elucidating the genetic influences on LA size would help to identify subjects at risk for developing an enlarged LA. In addition, this knowledge is essential for understanding cardiac structure and function at the molecular level and identifying therapeutic targets in the management of LA enlargement.Little is known about the genetic basis of LA size, with sparse studies mainly among Caucasian populations. [13][14][15][16][17] Therefore, we estimated the heritab...

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“…African Americans have a lower frequency of the CC genotype (∼3–10%) than both Europeans (∼20–30%) and Asians (∼7–12%), which may explain the intra-ancestral discrepancy in certain association studies [25], [30], [31], [52], [61]. Some of the previous studies focused on patient populations with cardiovascular diseases other than heart failure, and failed to find an association between −344CC genotype and AF [61], [62]. It is possible that aldosterone regulation plays a greater role in the pathogenesis of AF in heart failure patients than patients with other diseases considering the significant aldosterone involvement in the ventricular remodeling and cardiac fibrosis [14], [16], [19].…”

Section: Discussionmentioning

confidence: 99%

Association of Aldosterone Synthase Polymorphism (CYP11B2 -344T>C) and Genetic Ancestry with Atrial Fibrillation and Serum Aldosterone in African Americans with Heart Failure

et al. 2013

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The objective of this study was to examine the extent to which aldosterone synthase genotype (CYP11B2) and genetic ancestry correlate with atrial fibrillation (AF) and serum aldosterone in African Americans with heart failure. Clinical data, echocardiographic measurements, and a genetic sample for determination of CYP11B2 -344T>C (rs1799998) genotype and genetic ancestry were collected from 194 self-reported African Americans with chronic, ambulatory heart failure. Genetic ancestry was determined using 105 autosomal ancestry informative markers. In a sub-set of patients (n = 126), serum was also collected for determination of circulating aldosterone. The CYP11B2 −344C allele frequency was 18% among the study population, and 19% of patients had AF. Multiple logistic regression revealed that the CYP11B2 −344CC genotype was a significant independent predictor of AF (OR 12.7, 95% CI 1.60–98.4, p = 0.0150, empirical p = 0.011) while holding multiple clinical factors, left atrial size, and percent European ancestry constant. Serum aldosterone was significantly higher among patients with AF (p = 0.036), whereas increased West African ancestry was inversely correlated with serum aldosterone (r = −0.19, p = 0.037). The CYP11B2 −344CC genotype was also overrepresented among patients with extreme aldosterone elevation (≥90th percentile, p = 0.0145). In this cohort of African Americans with chronic ambulatory heart failure, the CYP11B2 −344T>C genotype was a significant independent predictor of AF while holding clinical, echocardiographic predictors, and genetic ancestry constant. In addition, increased West African ancestry was associated with decreased serum aldosterone levels, potentially providing an explanation for the lower risk for AF observed among African Americans.

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Functional polymorphisms in ACE and CYP11B2 genes and atrial fibrillation in patients with hypertensive heart disease

Abstract: Our study suggests that ACE I/D polymorphism is associated with AF and the DD genotype may be an independent predictive factor for AF in patients with hypertensive heart disease.

Cited by 18 publications

References 37 publications

Polymorphisms of Renin-Angiotensin-Aldosterone System Gene in Chinese Han Patients with Nonfamilial Atrial Fibrillation

Polymorphisms of Renin-Angiotensin-Aldosterone System Gene in Chinese Han Patients with Nonfamilial Atrial Fibrillation

A Comprehensive Genetic Study on Left Atrium Size in Caribbean Hispanics Identifies Potential Candidate Genes in 17p10

Association of Aldosterone Synthase Polymorphism (CYP11B2 -344T>C) and Genetic Ancestry with Atrial Fibrillation and Serum Aldosterone in African Americans with Heart Failure

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